This proposal will not only advance the knowledge of circadian rhythms and nocturnal asthma, but it will also prepare and nurture Dr. Brandon Lu for a successful career in academic research medicine. From the distinguished core of circadian rhythms and asthma researchers at Northwestern University, Dr. Lu can learn and apply the methods necessary to study circadian rhythms in a disease model that has interested him from his clinical training in Pulmonary Medicine. Through classwork in the K23 sponsored Master of Science in Clinical Investigation Program, Dr. Lu has acquiring skills in design, implementation, and analysis of research studies. Dr. Lu plans to further enrich his research skills with advanced courses in clinical research and seminars in circadian research during the grant period to prepare for future studies aimed at elucidating the role of the molecular clock machinery in nocturnal asthma and other medical diseases. Nocturnal asthma (NA)is a significant cause of morbidity and mortality from asthma. While the diurnal nature of the disease has been shown, the circadian basis of NA has not been well established. This project will determine the effects of the endogenous circadian rhythm on lung function in subjects with NA, non-NA, and healthy controls by employing a constant routine protocol to minimize the impact of exogenous factors(i.e. sleep, light, activity, etc.). The circadian rhythms of inflammation, the autonomic nervous system, and surrogates of central and peripheral endogenous circadian rhythm (melatonin and core clock gene cycling) will also be determined. We will determine if alterations in circadian rhythm (difference in phase or amplitude) exist in NA and whether these changes are related to the phenotype of NA. This proposal will reveal the pathophysiology of NA as it relates to the circadian system and allow future studies to develop novel therapies for NA that target the circadian system. It can also lead to improved identification of individuals predisposed to NA which can decrease the burden of NA on society. Together with a dedicated mentoring team, a committed researcher, and a well-designed plan, this proposal will propel Dr. Lu into an independent career in patient-oriented research.